Isl1 Directly Controls a Cholinergic Neuronal Identity in the Developing Forebrain and Spinal Cord by Forming Cell Type-Specific Complexes

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Neurons utilize various chemicals to transmit signals to a target cell. Distinct types of neurons in the spinal cord and forebrain, collectively termed cholinergic neurons, utilize the same chemical, acetylcholine, for signal transmission. These neurons play critical roles in controlling locomotion and cognition. In this study, we have found that the Isl1 gene orchestrates the process to generate cholinergic neurons in the spinal cord and forebrain. Isl1 forms two different types of multi-protein complexes in the spinal cord and forebrain. Both complexes bind the same genomic regions in a group of genes critical for cholinergic signal transmission, and promote their simultaneous expression. These cholinergic genes include enzymes that synthesize acetylcholine and proteins required to package acetylcholine into vesicles. The Isl1-containing multi-protein complexes were able to trigger the generation of cholinergic neurons in embryonic stem cells and neural stem cells. Our study reveals crucial mechanisms to coordinate the expression of genes in the same biological pathway in different cell types. Furthermore, it suggests a new strategy to produce cholinergic neurons from stem cells.

Vyšlo v časopise: Isl1 Directly Controls a Cholinergic Neuronal Identity in the Developing Forebrain and Spinal Cord by Forming Cell Type-Specific Complexes. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004280
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004280

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